I learned more about my bleeding disorders from whole genome sequencing

Speaking at the Hemophilia Federation of America’s Mild Matters Summit last year, former Hemophilia News Today columnist Shellye Horowitz shared how her treatment plan changed after she researched the genetic variant that caused her hemophilia A. Although she’s classified as “mild,” her factor treatment wasn’t effective enough to combat her bleeding.

Horowitz found extensive research on her specific variant, which is known to cause reduced binding of factor VIII to von Willebrand factor, resulting in faster clearance from the body, greater inhibitor risks, and challenges controlling bleeding. Furthermore, her variant doesn’t respond to DDAVP (desmopressin), a treatment used to help stop bleeding in patients with mild hemophilia A or von Willebrand disease type 1. Armed with this knowledge, she had an informed discussion with her hematologist and improved her treatment plan.

Genotyping for hemophilia isn’t yet standard in the U.S., but is routine in Australia, Iceland, and the U.K. Previously, people in the U.S. with hemophilia and suspected carriers could get genotype tested for free through the My Life Our Future project, which completed enrollment in 2017, but has provided researchers with valuable data.

The mystery of how I ended up with hemophilia B, which features low levels of clotting factor IX, has always puzzled me. Hemophilia doesn’t run in my family, so when my first hematologist suggested it might be the result of a spontaneous genetic variant, I was taken aback. I was only 10, so I had no idea what that meant, nor did my family. Another doctor, a rheumatologist, speculated it could be an autoimmune issue.

My path to genetic testing

Last year, I underwent whole genome sequencing through a commercial kit I purchased online. I was only somewhat surprised when the test revealed a genetic variant related to hemophilia B, explaining my mild hemophilia diagnosis and confirming I am a hemophilia B carrier.

The testing also hinted at a potential rare platelet disorder, prompting my hematologist to suggest I enroll in the ATHN 10 study, which includes genetic testing for various rare bleeding disorders, including hemophilia B. I enrolled, but am still awaiting the results, which could take up to 10 months.

Delving into my identified hemophilia B variant, I learned it was first reported in 1989. Most people with the variant are classified as having mild hemophilia based on factor IX levels in their blood. I’m curious if any identified cases include women.

Women, genetic variants, and factor levels remain poorly understood. Jill Johnsen, MD, an associate professor of hematology and oncology at the University of Washington, is investigating how genes and factor levels affect bleeding in women. In 2022, she told Bloodworks, a medical laboratory company, that, “we have lots of reason from prior work to know that in women, the [factor] level doesn’t correlate with bleeding like it does in men, and we don’t have a great explanation, but what does correlate is that they have the genetic change that causes hemophilia.”

Have you discovered your genotype yet? It might be worth finding out